Role for malic enzyme, pyruvate carboxylation, and mitochondrial malate import in glucose-stimulated insulin secretion
AUTOR(ES)
Heart, Emma
FONTE
American Physiological Society
RESUMO
Pyruvate cycling has been implicated in glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. The operation of some pyruvate cycling pathways is proposed to necessitate malate export from the mitochondria and NADP+-dependent decarboxylation of malate to pyruvate by cytosolic malic enzyme (ME1). Evidence in favor of and against a role of ME1 in GSIS has been presented by others using small interfering RNA-mediated suppression of ME1. ME1 was also proposed to account for methyl succinate-stimulated insulin secretion (MSSIS), which has been hypothesized to occur via succinate entry into the mitochondria in exchange for malate and subsequent malate conversion to pyruvate. In contrast to rat, mouse β-cells lack ME1 activity, which was suggested to explain their lack of MSSIS. However, this hypothesis was not tested. In this report, we demonstrate that although adenoviral-mediated overexpression of ME1 greatly augments GSIS in rat insulinoma INS-1 832/13 cells, it does not restore MSSIS, nor does it significantly affect GSIS in mouse islets. The increase in GSIS following ME1 overexpression in INS-1 832/13 cells did not alter the ATP-to-ADP ratio but was accompanied by increases in malate and citrate levels. Increased malate and citrate levels were also observed after INS-1 832/13 cells were treated with the malate-permeable analog dimethyl malate. These data suggest that although ME1 overexpression augments anaplerosis and GSIS in INS-1 832/13 cells, it is not likely involved in MSSIS and GSIS in pancreatic islets.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2692397Documentos Relacionados
- Engineering of glucose-stimulated insulin secretion and biosynthesis in non-islet cells.
- 13C NMR isotopomer analysis reveals a connection between pyruvate cycling and glucose-stimulated insulin secretion (GSIS)
- The Effect of Gastrin on Basal- and Glucose-Stimulated Insulin Secretion in Man
- Cholesterol Regulates Glucose-stimulated Insulin Secretion through Phosphatidylinositol 4,5-Bisphosphate*
- Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat.